The present invention relates generally to antibodies to biological mediators of immune function. More specifically, it is concerned with antibodies to a purified and isolated leukocyte chemotactic protein released by injured tissue (hereinafter NOURIN-I).
Biological mediators such as leukocyte chemotactic factors stimulate the migration of neutrophils from circulation into sites of infection or tissue damage. These mediators are also believed to increase cell adhesion to injured sites and to activate neutrophils to release toxic agents such as oxygen metabolites and proteases. Due to their important role, the nature and source of these mediators have been extensively studied. It has been believed they are primarily derived from low molecular weight serum protein components, that is, from complement-split products C3a and C5a and fibrin-split peptide products as well as from activated immune cells such as leukotriene B.sub.4, LTB.sub.4, and interleukin-8, IL-8. Type I collagen peptide products and the synthetic tripeptide f-Met-Leu-Phe are also chemotactically active for both neutrophils and mononuclear cells.
However, the initial signals that recruit and activate the neutrophils have not been defined and it is not known whether injured tissue directly participates in the influx of circulating leukocytes by releasing mediators which recruit neutrophils to the sites of the injury.
It has now been found, as described in my copending application Ser. No. 07/975,640 filed Nov. 13, 1992, now U.S. Pat. No. 5,403,914 that a high level of neutrophil chemotactic factor is released by tissues such as coronary arteries and myocardial tissue under ischemic conditions. In addition to the cardiovascular-derived neutrophil chemotactic factors, substantially the same factor has been detected in spinal cord, brain, cornea, retina, conjunctiva, stomach, vein grafts and urinary bladder. This neutrophil chemoattractant is believed to represent the "initial signal" that recruits neutrophils to the tissue shortly after injury induced chemical agents, physical trauma, ischemia, and endotoxin treatments. They differ in their biochemical characteristics and molecular weight from previously known factors, such as the complement split products C3a and C5a having molecular weights of about 11,000 daltons (11 KDa) and leukocyte products such as IL-8 and LTB.sub.4 that have molecular weights of 10 KDa and 366 Da, respectively. As released from the tissue, the factor exists as a protein complex having a molecular weight of about 100 KDa to 300 KDa. The complex is a positively charged unit consisting of a weakly associated high molecular weight co-factor or carrier and a low molecular weight greater than 500 Da, but less than 5 KDa, active factor that carries an apparent neutral or negative charge. From sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SES-PAGE) analysis, the purified protein (NOURIN-I) corresponding to the chemotactively active band has a molecular weight of 3 KDa. The protein has an isoelectric point of pH 7-8 for the cardiac derived factor, while the cornea-derived factor has a slightly higher isoelectric point of pH 8.5. It is clearly different from the previously known factors C3a, C5a, IL-8 and LTB.sub.4 which appear to play important roles as "late signals" that recruit additional neutrophils to infarcted myocardium and to regions where activated neutrophils exist, such as inflamed myocardium.